Implementation of phase III registration trials typically involves multiple partners, creating the risks that key activities are not completed or that partners duplicate efforts. It is therefore essential to clearly delineate roles and responsibilities at the start of the trial, and systematically oversee partner activities.
In STREAM, the trial Sponsor retained responsibility for oversight of investigational medicinal product but delegated most other activities to partners - MRC CTU at UCL for overall trial coordination and management, clinical oversight, data management, and statistical analysis; a CRO for regular onsite monitoring and source data verification; a central laboratory for safety testing; and ITM for central microbiology assessments and local monitoring.
There were a number of examples when the roles and responsibilities of partners were not clear, leading to inefficiencies in implementation. For example, at the start of Stage 2 of the trial, roles and responsibilities between MRC CTU at UCL and the CRO were not well documented, making it unclear who had ultimate responsibility (and therefore decision-making power) for overall site management. This arose in part because the “typical” CRO role in industry sponsored trials would have been more expansive than its role in STREAM. Until those roles were clearly delineated and documented, sites sometimes received conflicting instructions from MRC CTU at UCL and the CRO, which was inefficient and time consuming to manage.
Roles and responsibilities with respect to oversight of ITM were also unclear as between the sponsor and MRC CTU at UCL at the start of the trial. When the issue was identified, a microbiology sub-committee – made up of members from Vital Strategies, MRC CTU at UCL, and ITM – was formed. The committee regularly reviews a range of microbiology topics, including quality issues at site level laboratories, sample tracking (to ensure samples were arriving at ITM), and technical issues related to ITM’s central laboratory testing. The committee also developed and tracked key performance metrics to systematically assess progress on the trial. Because this subcommittee included members with responsibility for project management, vendor management and technical matters, it was an excellent model for ensuring coordinated oversight of a key trial activity.